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Chronic Kidney Disease
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Aldosterone Antagonists for Preventing the Progression of Chronic Kidney Disease: A Systematic Review and Meta-analysis

Sankar D. Navaneethan, Sagar U. Nigwekar, Ashwini R. Sehgal and Giovanni F.M. Strippoli
CJASN March 2009, 4 (3) 542-551; DOI: https://doi.org/10.2215/CJN.04750908
Sankar D. Navaneethan
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Sagar U. Nigwekar
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Ashwini R. Sehgal
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Giovanni F.M. Strippoli
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    Figure 1.

    Flow chart showing the number of citations retrieved by individual searches and number of trials included in the systematic review.

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    Figure 2.

    Effect of aldosterone antagonists plus ACEi and/or ARB compared with ACEI and/or ARB alone on the end of treatment proteinuria.

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    Figure 3.

    Effect of aldosterone antagonists plus ACEi and/or ARB compared with ACEI and/or ARB alone on the end of treatment GFR.

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    Figure 4.

    Incidence of hyperkalemia with aldosterone antagonists plus ACEi and/or ARB in comparison to ACEI and/or ARB alone.

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    Table 1.

    Characteristics of the populations and interventions in the included trials of aldosterone antagonistsa

    StudyBaseline kidney diseaseBaseline proteinuria (in g/24 h) or UACR (mean +/− SD)Baseline renal function (ml/min/1.73 m2)No. of patientsInterventionCo-intervention in treatment arm(n) (ACEI and/or ARB)Study duration (months)Study end points
    Bianchi 2006 (23)Idiopathic GNTreatment: 2.1+/−0.08 Control: 2.0+/−0.0762.3 +/− 1.6165Spirinolactone 25 mg dailyACEI alone: 29 ARB alone: 17 ACEI + ARB: 371224 h proteinuria, BP, serum creatinine, eGFR, hyperkalemia, gynecomastia
    Chrysostomou 2006b (24)Diabetic and non-diabetic nephropathyACEI alone: 2.6+/− 1.6 ACEI + ARB: 2.5 +/− 1.8 ACEI + Spirinolactone: 2.2+/−1.4 ACEI + ARB + Spirinolactone: 3.1+/− 1.9ACEI alone: 81.6 ACEI + ARB: 68.0 ACEI + Spirinolactone: 59.4 ACEI + ARB + Spirinolactone: 57.641Spirinolactone 25 mg dailyACEI alone: 10 ACEI + ARB: 10 ACEI + Spirinolactone: 10 ACEI + ARB + Spiriniloactone: 116Primary: 24 h proteinuria Secondary: BP, serum creatinine, Cockraft-Gault creatinine clearance hyperkalemia
    Epstein 2002 (37)Diabetic nephropathy (Type 2)NANA215EPL 200 mg/d vs. ACEI 40 mg/d vs. EPL 200 mg/d + ACEI 10 mgNA624 h proteinuria, BP, serum creatinine, eGFR, hyperkalemia, gynaecomastia
    Epstein 2006 (25)Diabetic nephropathy (Type 2)UACR Treatment 50 mg: 422 100 mg: 240 Control: 280Eplerenone 50 mg: 91 100 mg: 86 Control: 91268EPL 50 mg and 100 mg dailyACEI: 26812Primary: Percentage change in UACR, incidence of hyperkalemia Secondary: change in BP, eGFR, adverse events, gynaecomastia
    Furamatsu 2008 (35)Non-diabetic nephropathy> 0.5 g/day (both groups) u-Prot/u-Cr (g/g·Cr) Treatment: 1.42 ±0.28 Control: 1.44 ±0.28Treatment: 91.8 ±11.8 Control: 68.9 ±7.830Spirinolactone 25 mg dailyACEI + ARB: 3012Primary: Reduction in proteinuria Secondary: BP, Cockraft-Gault creatinine clearance, hyperkalemia, gynaecomastia
    Rachmani 2004 (33)Diabetic nephropathy (Type 2)UACR Treatment: 456 mg/g Control: 451 mg/gSerum creatinine >160 mmol/l46Spirinolactone 100 mg daily and decreased to 50 mg dailyNA20UACR, BP, serum creatinine, hyperkalemia
    Rossing 2005c (26)Diabetic nephropathy (Type 2)>300 mg/24 hGFR > 3021Spirinolactone 25 mg dailyNA224 h albuminuria, BP, GFR (based on EDTA), hyperkalemia,
    Schjoedt 2005c (27)Diabetic nephropathy (Type 1)>300 mg/24 hGFR >3020Spirinolactone 25 mg dailyNA2Primary: 24 h albuminuria Secondary: BP, serum creatinine, GFR (based on EDTA), hyperkalemia, gynaecomastia
    Schjoedt 2006c (34)Diabetic nephropathy (Type 1 and 2)>2.5 g/24 hGFR >3020Spirinolactone 25 mg daily224 h albuminuria, BP, serum creatinine, GFR (based on EDTA), hyperkalemia
    Tylicki 2008 (36)Non-diabetic nephropathy0.97 ±0.18 at the randomization pointMean GFR 107.8 (93-140.9)18Spirinolactone 25 mg dailyACEI + ARB: 182Primary: 24 h proteinuria Secondary: BP, Cockraft-Gault creatinine clearance, hyperkalemia
    Van den Meiracker 2006 (32)Diabetic nephropathy (Type 2)Treatment: 0.7 Control: 1.0Treatment: 87 Control: 6453Spirinolactone 50 mg dailyACEI: 17 ARB: 71224 h proteinuria, BP, serum creatinine, eGFR, hyperkalemia, gynecomastia
    • ↵a UACR, Urine Albumin Creatinine Ratio; ACEI, Angiotensin-Converting Enzyme Inhibitor; ARB, Aldosterone Receptor Blocker; GFR, Glomerular Filtration Rate; BP, Blood Pressure; NA, Not available; EPL, Eplerenone; GN, Glomerulonephritis.

    • ↵b This study had 4 arms.

    • ↵c These studies did not report the exact number of patients who had ACEi and/or ARB in treatment and control arm separately.

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Clinical Journal of the American Society of Nephrology
Vol. 4, Issue 3
March 2009
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Aldosterone Antagonists for Preventing the Progression of Chronic Kidney Disease: A Systematic Review and Meta-analysis
Sankar D. Navaneethan, Sagar U. Nigwekar, Ashwini R. Sehgal, Giovanni F.M. Strippoli
CJASN Mar 2009, 4 (3) 542-551; DOI: 10.2215/CJN.04750908

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Aldosterone Antagonists for Preventing the Progression of Chronic Kidney Disease: A Systematic Review and Meta-analysis
Sankar D. Navaneethan, Sagar U. Nigwekar, Ashwini R. Sehgal, Giovanni F.M. Strippoli
CJASN Mar 2009, 4 (3) 542-551; DOI: 10.2215/CJN.04750908
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